PB2034: CAMMA 1: A MULTICENTER PHASE IB TRIAL EVALUATING THE SAFETY, PHARMACOKINETICS AND ACTIVITY OF CEVOSTAMAB-CONTAINING REGIMENS IN PATIENTS WITH RELAPSED OR REFRACTORY MULTIPLE MYELOMA
Authors: R. Vij, H. Schade, S. Trudel, A. C. Chang, J. Huang, D. Samineni, T. Sumiyoshi, J. Tsai, T. Wong, S. J. Harrison
Journal: HemaSphere (2022)

Background: Treatment of relapsed/refractory (R/R) multiple myeloma (MM) is challenging, especially in later lines where drug resistance reduces therapeutic options and remission duration. Prognosis is poor (estimated survival: <1 year) for patients with MM who have received >3 prior lines of therapy and are triple refractory to immunomodulatory drugs (IMiDs), proteasome inhibitors (PIs) and anti-CD38 agents (Gandhi et al. 2019). Thus R/R MM constitutes a significant unmet medical need. Fragment crystallizable receptor-like 5 (FcRH5) is expressed on myeloma cells with near 100% prevalence (Li et al. 2017), constituting a novel therapeutic target. Cevostamab is an IgG1-based T-cell-engaging bispecific antibody engineered to target the most membrane-proximal domain of FcRH5 on myeloma cells and cluster of differentiation 3 (CD3) on T-cells, resulting in T-cell killing of myeloma cells. Clinical data from the first-in-human Phase I study (GO39775) suggest that cevostamab monotherapy is highly active in heavily pre-treated patients with R/R MM, with an overall response rate of 56.7% at the 132–198mg dose level (Trudel et al. ASH 2021 Oral presentation). Thus, cevostamab's activity and safety profile support further development. Due to their stimulatory effects on T-cell activity, combination of cevostamab with anti-myeloma agents (pomalidomide [P] or daratumumab [D]) may be synergistic, offering the potential to further improve efficacy. Aims: To evaluate the safety, tolerability, pharmacokinetics (PK) and pharmacodynamics of cevostamab-containing combination regimens (Arm B: cevostamab plus P and dexamethasone [d] [Pd]; Arm C: cevostamab plus Dd) in patients with R/R MM. A modified weekly schedule for cevostamab is also under investigation (Arm A: cevostamab monotherapy). Methods: CAMMA 1 (NCT04910568) is an open-label, multicentre Phase Ib trial in patients with R/R MM. Patients must be aged ≥18 years, have an Eastern Cooperative Oncology Group Performance Status of 0 or 1 and a life expectancy of >12 weeks. Patients in all arms have R/R MM; Arms B and C include patients with prior IMiD and PI exposure. Patients with prior CAR-T therapy may enroll with a washout period of 12 weeks post-CAR-T infusion. Cevostamab is administered by intravenous infusion q1w (C1–2)/q2w (C3–6)/q4w (C7–13) in Arm A, q2w (C1–6)/q4w (C7+) in Arm B, and q3w (C1–8)/q4w (C9+) in Arm C. Each arm consists of a safety run-in and an expansion cohort. The primary objective is to evaluate the safety and tolerability of cevostamab plus Pd, cevostamab plus Dd and cevostamab monotherapy. Secondary objectives include assessment of activity, PK, immunogenicity, and pharmacodynamic biomarkers. Results: Enrolment for Arm A is ongoing, with patients receiving up to 13 treatment cycles. Arms B and C are planned; patients will receive treatment until disease progression or unacceptable toxicity. All patients must provide informed consent. Summary/Conclusion: CAMMA 1 is an ongoing study of cevostamab plus Pd, cevostamab plus Dd and cevostamab monotherapy in patients with R/R MM. Further study details will be presented.